Hydrophobic drugs, i.e., drugs having poor solubility in aqueous solution, present difficult formulation problems for effective administration to patients. A well-designed formulation must, at a minimum, be capable of presenting a therapeutically-effective amount of the hydrophobic drug to the desired absorption site, in an absorbable form. Even this minimal functionality is difficult to achieve with hydrophobic drugs because of the slow disintegration or dissolution. Especially in intestinal fluid, a drug that does not dissolve sufficiently cannot pass via the intestinal wall membrane into the bloodstream, and is simply excreted by the individual via their intestinal tract without providing a therapeutic benefit.
An example of a hydrophobic drug is ziprasidone, also known as 5-[2-[4-(1,2-benzisothiazol-3-yl)-1-piperazinyl]ethyl]-6-chloro-1,3-dihydro-2H-indol-2-one. Ziprasidone is described in U.S. Pat. Nos. 4,831,031 and 5,312,925. Ziprasidone is an antipsychotic drug indicated for the treatment of schizophrenia. The empirical formula of C21H21ClN4OS (free base of ziprasidone) has the following structural formula:

Ziprasidone capsules contain a monohydrochloride, monohydrate salt of ziprasidone. Chemically, ziprasidone hydrochloride (HCl) monohydrate is 5-[2-[4-(1,2-benzisothiazol-3-yl)-1-piperazinyl]ethyl]-6-chloro-1,3-dihydro-2H-indol-2-one, monohydrochloride, monohydrate. The empirical formula is C21H21ClN4OS HCL H2O. Ziprasidone capsules are commercially-available from Pfizer under the trademark Geodon® capsules and contain ziprasidone HCl monohydrate, lactose, pre-gelatinized starch and magnesium stearate.
U.S. Pat. No. 6,150,366 describes compositions containing crystalline ziprasidone free base or crystalline ziprasidone HCl particles having a mean particle size equal to or less than about 85 microns and a pharmaceutically acceptable diluent or carrier.
It would be desirable to improve the solubility of hydrophobic drug containing compositions without necessarily employing such conventional methods as milling or micronizing the drug in order to increase solubility.